Multimodal Imaging Group, Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada.
Institute of Medical Science, University of Toronto, Toronto, ON, Canada.
Schizophr Bull. 2017 Jul 1;43(4):764-777. doi: 10.1093/schbul/sbw221.
Kynurenic acid (KYNA) is an endogenous antagonist of N-methyl-D-aspartate and α7 nicotinic acetylcholine receptors that is derived from astrocytes as part of the kynurenine pathway of tryptophan degradation. Evidence suggests that abnormal KYNA levels are involved in the pathophysiology of schizophrenia. However, this has never been assessed through a meta-analysis. A literature search was conducted through Ovid using Embase, Medline, and PsycINFO databases (last search: December 2016) with the search terms: (kynuren* or KYNA) and (schizophreni* or psychosis). English language studies measuring KYNA levels using any method in patients with schizophrenia and healthy controls (HCs) were identified. Standardized mean differences (SMDs) were calculated to determine differences in KYNA levels between groups. Subgroup analyses were separately performed for nonoverlapping participant samples, KYNA measurement techniques, and KYNA sample source. The influences of patients' age, antipsychotic status (%medicated), and sex (%male) on study SMDs were assessed through a meta-regression. Thirteen studies were deemed eligible for inclusion in the meta-analysis. In the main analysis, KYNA levels were elevated in the patient group. Subgroup analyses demonstrated that KYNA levels were increased in nonoverlapping participant samples, and centrally (cerebrospinal fluid and brain tissue) but not peripherally. Patients' age, %medicated, and %male were each positively associated with study SMDs. Overall, KYNA levels are increased in patients with schizophrenia, specifically within the central nervous system. An improved understanding of KYNA in patients with schizophrenia may contribute to the development of novel diagnostic approaches and therapeutic strategies.
犬尿酸（KYNA）是一种内源性 N-甲基-D-天冬氨酸和 α7 烟碱型乙酰胆碱受体拮抗剂，作为色氨酸降解的犬尿氨酸途径的一部分，由星形胶质细胞产生。有证据表明，异常的 KYNA 水平与精神分裂症的病理生理学有关。然而，这从未通过荟萃分析进行过评估。通过 Ovid 使用 Embase、Medline 和 PsycINFO 数据库进行文献检索（最后一次搜索：2016 年 12 月），使用的检索词为：（犬尿氨酸或 KYNA）和（精神分裂症或精神病）。确定了使用任何方法在精神分裂症患者和健康对照者（HCs）中测量 KYNA 水平的英语语言研究。计算标准化均数差值（SMD）以确定组间 KYNA 水平的差异。分别对非重叠参与者样本、KYNA 测量技术和 KYNA 样本来源进行亚组分析。通过荟萃回归评估患者年龄、抗精神病药物状态（%用药）和性别（%男性）对研究 SMD 的影响。13 项研究被认为符合纳入荟萃分析的条件。在主要分析中，患者组的 KYNA 水平升高。亚组分析表明，非重叠参与者样本中的 KYNA 水平升高，且在中枢（脑脊液和脑组织）而不是外周。患者年龄、%用药和%男性均与研究 SMD 呈正相关。总体而言，精神分裂症患者的 KYNA 水平升高，特别是在中枢神经系统内。对精神分裂症患者中 KYNA 的更好理解可能有助于开发新的诊断方法和治疗策略。
